Search

Abstract Parkinson’s disease (PD) and multiple system atrophy (MSA) can be preceded by isolated REM sleep behavior disorder (iRBD). As excessive sighing during wakefulness is a red flag for MSA in individuals with parkinsonism, we measured sighing during slow wave sleep (N3) and REM sleep as potential biomarkers in 73 participants with MSA, 111 with iRBD, 257 with PD, and 115 controls. The number of sighs/hour of N3 (index) was higher in the MSA group than in the other groups. Sighs were rarer in REM sleep than in N3 sleep. A sigh index greater than 3.4/h of N3 was 95% sensitive in discriminating participants with MSA from controls, and a sigh index greater than 0.8 sigh/h of REM sleep was 87% specific in discriminating participants with MSA from controls. MSA participants with (vs. without) sigh were younger, had a lower apnea-hypopnea index (but no more stridor), and had no other difference in motor, autonomic, cognitive, and sensory symptoms. The sigh index could be used for screening for MSA in the millions of middle-aged persons who receive polysomnography for other purposes. Whether sighing in iRBD predicts preferential conversion towards MSA should be measured in a longitudinal study.

Abstract Background Morphine relieves dyspnea in various clinical circumstances. Whether or not this applies to patients admitted to intensive care units (ICUs) for acute respiratory failure (ARF) is unknown. We evaluated the efficacy and safety of low-dose morphine on dyspnea in patients admitted to the ICU for ARF. Methods In this single-center, double-blind, phase 2, randomized, controlled trial, we assigned non-intubated adults admitted to the ICU for ARF with severe dyspnea, defined by a visual analog scale for dyspnea (dyspnea-VAS) from zero (no dyspnea) to 100 mm (worst imaginable dyspnea) ≥40 mm, to receive a low dose of Morphine Hydrochloride (intravenous titration followed by subcutaneous relay) or Placebo. All patients received standard therapy, including etiological treatment and non-invasive respiratory support. Results Twenty-two patients were randomized, 11 in each group. The average dyspnea (median [interquartile range]) over 24 hours did not significantly differ between the two groups (40 [25 – 43] mm in the Morphine group vs. 40 [36 – 49] mm in the Placebo group, p=0.411). Dyspnea-VAS was lower in the Morphine group than in the Placebo group at the end of intravenous titration (30 [11 – 30] vs. 35 [30 – 44], p=0.044) and four hours later (18 [10 – 29] vs. 50 [30 – 60], p=0.043). The cumulative probability of intubation was higher in the Morphine group than in the Placebo group (p=0.046) Conclusion In this phase 2 pilot trial, morphine did not improve 24-hour average dyspnea in adult patients with ARF, even though it had a statistically significant immediate effect. Of concern, Morphine use was associated with a higher intubation rate. Trial registration The protocol was declared on the ClinicalTrial.gov database (no. NCT04358133) and was published in September 2022.

Abstract After a fortuitous observation of two cases of chemosensitivity recovery in women with congenital central hypoventilation syndrome (CCHS) who took desogestrel, we aimed to evaluate the ventilatory response to hypercapnia of five CCHS patients with or without treatment consisting of desogestrel (DESO) or levonorgestrel (LEVO). Only two patients became responsive to hypercapnia under treatment, according to their basal vagal heart rate variability. These results suggest that heart rate variability may be promising tool to discriminate patients susceptible to become responsive to hypercapnia under DESO-LEVO treatment. Clinical Trials Identifier NCT01243697

Abstract Background Dyspnea conveys an upsetting or distressing experience of breathing awareness. It heavily weighs on chronic respiratory disease patients, particularly when it persists despite maximal treatment of causative abnormalities. The physical, psychological and social impacts of persistent dyspnea are ill-appreciated by others. This invisibility constitutes a social barrier and impedes access to care. This study aimed to better understand dyspnea invisibility in patients with chronic obstructive pulmonary disease (COPD) through quantitative discourse analysis. Methods We conducted a lexicometric analysis (lemmatization, descending hierarchical classification, multicomponent analysis, similarity analysis) of 11 patients' discourses (6 men, severe COPD; immediate postexacerbation rehabilitation) to identify semantic classes and communities, which we then confronted with themes previously identified using interpretative phenomenological analysis (IPA). Results Class#1 ("experience and need for better understanding"; 38.9% of semantic forms, 50% of patients) illustrates the gap that patients perceive between their experience and what others see, confirming the importance of dyspnea invisibility in patients' concerns. Class#2 ("limitations"; 28.7% of forms) and Class#3 (management"; 13.1% of forms) point to the weight of daily limitations in performing basic activities, of the need to accept or adapt to the constraints of the disease. These three classes matched previously identified IPA-derived themes. Class#4 ("hospitalization"; 18.2% of forms) points to the importance of interactions with the hospital, especially during exacerbations, which constitutes novel information. Conclusions Lexicometry confirms the importance of dyspnea invisibility as a burden to COPD patients.

Introduction Disability, resulting from altered interactions between individuals and their environment, is a worldwide issue causing inequities and suffering. Many diseases associated with breathlessness cause disability but the relationship between disability and the severity of breathlessness itself is unknown.This study evaluated associations between disability using the WHO’s Disability Assessment Schedule (WHODAS) 2.0 and levels of long-term breathlessness limiting exertion.Methods This population-based, cross-sectional online survey (n=10 033) reflected the most recent national census (2016) by age, sex, state/territory of residence and rurality. Assessments included self-reported disability (WHODAS 2.0 12-item (range 12 (no disability) to 60 (most severe disability)) assessed in 6 domains) and long-term breathlessness limiting exertion (modified Medical Research Council (mMRC) breathlessness scale; 0–4 (4—most severe)). Days in the last month affected by breathlessness were reported.Results Of respondents (52% women; mean age 45), mean total disability score was 20.9 (SD 9.5). 42% (n=4245) had mMRC >0 (mMRC1 31% (n=3139); mMRC2 8% (n=806); mMRC3,4 3% (n=300)). Every level of long-term breathlessness limiting exertion was associated with greater levels of disability (total p

Physical examination of the thorax is key to the clinical diagnosis of respiratory diseases. Among other examination techniques, palpation evaluates the transmission of high-frequency vibrations produced by vocalizations (tactile fremitus), which helps the physicians to identify abnormalities within the respiratory system. We propose the use of an airborne ultrasound surface motion camera (AUSMC) to quantitatively map the vibrations induced by subject vocalization. This approach could make the examination of vocal fremitus quantifiable, reproducible, and archivable. Massive data collection of vocal fremitus could allow using artificial intelligence algorithms to isolate vibration patterns that could help disease identification. Until now, in contrast, the interpretation of vocal fremitus has been subject to the physician’s experience and remains subjective. In the present work, we demonstrate the capabilities of the AUSMC to measure vocal fremitus thoracic vibration maps on 77 healthy volunteers. We have observed a spatial dependence of vibration maps on vocalization frequency. We observed that the left lung generates fewer surface vibrations than the right one, which was expected according to their respective dimensions. We also discuss the implications of our findings.

Abstract Background Venovenous extracorporeal membrane oxygenation (VV ECMO) is frequently associated with deep sedation and neuromuscular blockades, that may lead to diaphragm dysfunction. However, the prevalence, risk factors, and evolution of diaphragm dysfunction in patients with VV ECMO are unknown. We hypothesized that the prevalence of diaphragm dysfunction is high and that diaphragm activity influences diaphragm function changes. Methods Patients with acute respiratory distress syndrome (ARDS) requiring VV ECMO were included in two centers. Diaphragm function was serially assessed by measuring the tracheal pressure in response to phrenic nerve stimulation (Ptr,stim) from ECMO initiation (Day 1) until ECMO weaning. Diaphragm activity was estimated from the percentage of spontaneous breathing ventilation and by measuring the diaphragm thickening fraction (TFdi) with ultrasound. Results Sixty-three patients were included after a median of 4 days (3–6) of invasive mechanical ventilation. Diaphragm dysfunction, defined by Ptr, stim ≤ 11 cmH2O, was present in 39 patients (62%) on Day 1 of ECMO. Diaphragm function did not change over the study period and was not influenced by the percentage of spontaneous breathing ventilation or the TFdi during the 1 week. Among the 63 patients enrolled in the study, 24 (38%) were still alive at the end of the study period (60 days). Conclusions Sixty-two percent of patients undergoing ECMO for ARDS related to SARS CoV-2 infection had a diaphragm dysfunction on Day 1 of ECMO initiation. Diaphragm function remains stable over time and was not associated with the percentage of time with spontaneous breathing. ClinicalTrials.gov Identifier NCT04613752 (date of registration February 15, 2021).

Abstract Patients with obstructive sleep apneas (OSA) do not complain from dyspnea during resting breathing. Placement of a mandibular advancement device (MAD) can lead to a sense of improved respiratory comfort (“pseudo‐relief”) ascribed to a habituation phenomenon. To substantiate this conjecture, we hypothesized that, in non‐dyspneic awake OSA patients, respiratory‐related electroencephalographic figures, abnormally present during awake resting breathing, would disappear or change in parallel with MAD‐associated pseudo‐relief. In 20 patients, we compared natural breathing and breathing with MAD on: breathing discomfort (transitional visual analog scale, VAS‐2); upper airway mechanics, assessed in terms of pressure peak/time to peak (TTP) ratio respiratory‐related electroencephalography (EEG) signatures, including slow event‐related preinspiratory potentials; and a between‐state discrimination based on continuous connectivity evaluation. MAD improved breathing and upper airway mechanics. The 8 patients in whom the EEG between‐state discrimination was considered effective exhibited higher Peak/TTP improvement and transitional VAS ratings while wearing MAD than the 12 patients where it was not. These results support the notion of habituation to abnormal respiratory‐related afferents in OSA patients and fuel the causative nature of the relationship between dyspnea, respiratory‐related motor cortical activity and impaired upper airway mechanics in this setting.

Abstract Background Patients who are admitted to the intensive care unit (ICU) for severe acute exacerbations of chronic obstructive pulmonary disease (COPD) have poor outcomes. Although international clinical practice guidelines cautiously recommend the routine use of systemic corticosteroids for COPD exacerbations, data are scarce and inconclusive regarding their benefit for most severe patients who require mechanical ventilation in the ICU. Furthermore, corticosteroids may be associated with an increased risk of infection, ICU-acquired limb weakness, and metabolic disorders. Methods and analysis This study is an investigator-initiated, multicentre, randomized, placebo-controlled, double-blind trial comparing systemic corticosteroids to placebo during severe acute exacerbations of COPD in patients who require mechanical ventilation in French ICUs. A total of 440 patients will be randomized 1:1 to methylprednisolone (1 mg/kg) or placebo for 5 days, and stratified according to initial mechanical ventilation (non-invasive or invasive), pneumonia as triggering factor, and recent use of systemic corticosteroids (

Background Immersive virtual reality (iVR)-based digital therapeutics are gaining clinical attention in the field of pain management. Based on known analogies between pain and dyspnoea, we investigated the effects of visual respiratory feedback on persistent dyspnoea in patients recovering from coronavirus disease 2019 (COVID-19) pneumonia. Methods We performed a controlled, randomised, single-blind, crossover proof-of-concept study (feasibility and initial clinical efficacy) to evaluate an iVR-based intervention to alleviate dyspnoea in patients recovering from COVID-19 pneumonia. Included patients reported persistent dyspnoea (≥5 on a 10-point scale) and preserved cognitive function (Montreal Cognitive Assessment score >24). Assignment was random and concealed. Patients received synchronous (intervention) or asynchronous (control) feedback of their breathing, embodied via a gender-matched virtual body. The virtual body flashed in a waxing and waning visual effect that could be synchronous or asynchronous to the patient's respiratory movements. Outcomes were assessed using questionnaires and breathing recordings. Results Study enrolment was open between November 2020 and April 2021. 26 patients were enrolled (27% women; median age 55 years, interquartile range (IQR) 18 years). Data were available for 24 of 26 patients. The median rating on a 7-point Likert scale of breathing comfort improved from 1 (IQR 2) at baseline to 2 (IQR 1) for synchronous feedback, but remained unchanged at 1 (IQR 1.5) for asynchronous feedback (p

Aim To compare prednisone and placebo for the treatment of outpatients treated for acute exacerbations of chronic obstructive pulmonary disease (COPD) in a primary care setting. Methods A multicentre, parallel, double-blind, pragmatic randomised controlled trial was performed in France. A total of 66 general practitioners included patients aged ≥40 years with cumulative smoking of ≥10 pack-years and a diagnosis of certain or likely acute exacerbation of COPD. Oral prednisone (40 mg) or placebo were administered daily for 5 days. The main outcome was treatment failure at 8 weeks, defined as a composite criterion based on the occurrence of at least one of the following: unplanned visit to an emergency department or to a practitioner in the ambulatory setting, hospital admission or death. The planned sample size was 202 patients per group. Results 175 patients were included from February 2015 to May 2017 (43% of the planned sample). All-cause 8-week treatment failure rate was 42.0% in the prednisone group and 34.5% in the placebo group (relative risk 1.22, 95% CI 0.87–1.69, p=0.25). Respiratory-related 8-week treatment failure rate was 27.6% in the prednisone group and 13.6% in the placebo group (relative risk 2.00, 95% CI 1.15–3.57, p=0.015). Conclusion Although the planned sample size was not achieved, the study does not suggest that oral corticosteroids are more effective than placebo for the treatment of an acute exacerbation of COPD in a primary care setting.

Alteration of posturo-respiratory coupling (PRC) may precede postural imbalance in patients with chronic respiratory disease. PRC assessment would be appropriate for early detection of respiratory-related postural dysfunction. PRC may be evaluated by respiratory emergence (REm), the proportion of postural oscillations attributed to breathing activity; assessed by motion analysis) as measured from the displacement of the center of pressure (CoP) (measured with a force platform). To propose a simplified method of PRC assessment (using motion capture only), we hypothesized that the REm can appropriately be measured derived from single body segment the postural oscillations of a single body segment rather than whole body postural oscillations. An optoelectronic system recorded the breathing pattern and the postural oscillations of six body segments in 50 healthy participants (22 women), 34 years [26; 48]. The CoP displacements were assessed using a force platform. One-minute recordings were made in standing position in four conditions by varying vision (eyes opened/closed) and jaw position (rest position/dental contact). The Sway Path and Mean Velocity of the CoP and of the representative point of each body segment were recorded. The REm was measured along the major and the minor axis of the 95% confidence ellipse of the CoP position (REm_MajorAxisCoP; REm_MinorAxisCoP) and of that of each body segment. SwayPathCoP and MVCoP varied widely across the four conditions (par< 0.000001). These changes were related to the visual condition ( $\text{p} < 0.000001$ ) while the jaw position had no effect. The REm_MajorAxisCoP and the REm_MinorAxisCoP changed across conditions ( $\text{p} < 0.05$ ); this was related to vision while jaw induced changes only for the REm_MinorAxisCoP. The SwayPath, the Mean Velocity and the REm of all body segments were significantly correlated to the CoP, but the highest correlations were observed for the thorax, the pelvis and the shoulder. PRC may be assessed from the postural oscillations of thorax, pelvis and shoulder. This should simplify the evaluation of respiratory-related postural interactions in the clinical environment, by using a single device to simultaneously assess postural oscillations on body segments, and breathing pattern. In addition, this study provides reference data for PRC and its sensory-related modulations on body segments along the postural chain.

Abstract Background Dyspnea is common and severe in intensive care unit (ICU) patients managed for acute respiratory failure. Dyspnea appears to be associated with impaired prognosis and neuropsychological sequels. Pain and dyspnea share many similarities and previous studies have shown the benefit of morphine on dyspnea in patients with end-stage onco-hematological disease and severe heart or respiratory disease. In these populations, morphine administration was safe. Here, we hypothesize that low-dose opioids may help to reduce dyspnea in patients admitted to the ICU for acute respiratory failure. The primary objective of the trial is to determine whether the administration of low-dose titrated opioids, compared to placebo, in patients admitted to the ICU for acute respiratory failure with severe dyspnea decreases the mean 24-h intensity of dyspnea score. Methods In this single-center double-blind randomized controlled trial with 2 parallel arms, we plan to include 22 patients (aged 18–75 years) on spontaneous ventilation with either non-invasive ventilation, high flow oxygen therapy or standard oxygen therapy admitted to the ICU for acute respiratory failure with severe dyspnea. They will be assigned after randomization with a 1:1 allocation ratio to receive in experimental arm administration of low-dose titrated morphine hydrochloride for 24 h consisting in an intravenous titration relayed subcutaneously according to a predefined protocol, or a placebo (0.9% NaCl) administered according to the same protocol in the control arm. The primary endpoint is the mean 24-h dyspnea score assessed by a visual analog scale of dyspnea. Discussion To our knowledge, this study is the first to evaluate the benefit of opioids on dyspnea in ICU patients admitted for acute respiratory failure. Trial registration ClinicalTrials.gov NCT04358133 . Registered on 24 April 2020.

Abstract Rationale Dyspnea, a key symptom of acute respiratory failure, is not among the criteria for spontaneous breathing trial (SBT) failure. Here, we sought (1) to determine whether dyspnea is a reliable failure criterion for SBT failure; (2) to quantify the relationship between dyspnea and the respective electromyographic activity of the diaphragm (EMGdi), the parasternal (EMGpa) and the Alae nasi (EMGan). Methods Mechanically ventilated patients undergoing an SBT were included. Dyspnea intensity was measured by the Dyspnea-Visual Analogic Scale (Dyspnea-VAS) at the initiation and end of the SBT. During the 30-min SBT or until SBT failure, the EMGdi was continuously measured with a multi-electrode nasogastric catheter and the EMGan and EMGpa with surface electrodes. Results Thirty-one patients were included, SAPS 2 (median [interquartile range]) 53 (37‒74), mechanically ventilated for 6 (3‒10) days. Seventeen patients (45%) failed the SBT. The increase in Dyspnea-VAS along the SBT was higher in patients who failed (6 [4‒8] cm) than in those who passed (0 [0‒1] cm, p = 0.01). The area under the receiver operating characteristics curve for Dyspnea-VAS was 0.909 (0.786–1.032). The increase in Dyspnea-VAS was significantly correlated to the increase in EMGan (Rho = 0.42 [0.04‒0.70], p

Abstract Background Whether dyspnea is present before starting a spontaneous breathing trial (SBT) and whether it may affect the outcome of the SBT is unknown. Mechanical Ventilation—Respiratory Distress Observation Scale (MV-RDOS) has been proposed as a reliable surrogate of dyspnea in non-communicative intubated patients. In the present study, we sought (1) to describe the evolution of the MV-RDOS during a SBT and (2) to investigate whether MV-RDOS can predict the outcome of the SBT. Methods Prospective, single-center study in a twenty-two bed ICU in a tertiary center. Patients intubated since more 48 h who had failed a first SBT were eligible if they meet classical readiness to wean criteria. The MV-RDOS was assessed before, at 2-min, 15-min and 30-min (end) of the SBT. The presence of clinically important dyspnea was inferred by a MV-RDOS value ≥ 2.6. Results Fifty-eight patients (age 63 [51–70], SAPS II 66 [51–76]; med [IQR]) were included. Thirty-three (57%) patients failed the SBT, whose 18 (55%) failed before 15-min. Twenty-five (43%) patients successfully passed the SBT. A MV-RDOS ≥ 2.6 was present in ten (17%) patients before to start the SBT. All these ten patients subsequently failed the SBT. A MV-RDOS ≥ 2.6 at 2-min predicted a SBT failure with a 51% sensibility and a 88% specificity (AUC 0.741 95% confidence interval [CI] 0.616–0.866, p = 0.002). Best cut-off value at 2-min was 4.3 and predicted SBT failure with a 27% sensibility and a 96% specificity. Conclusion Despite patients met classical readiness to wean criteria, respiratory distress assessed with the MV-RDOS was frequent at the beginning of SBT. Measuring MV-RDOS before to initiate a SBT could avoid undue procedure and reduce patient’s exposure to unnecessary mechanical ventilation weaning failure and distress.

Rationale Breathing is a cyclic activity that is variable by nature. Breathing variability is modified in mechanically ventilated patients. We aimed to evaluate whether decreased variability on the day of transition from assist-control ventilation to a partial mode of assistance was associated with a poorer outcome. Methods This was an ancillary study of a multicentre, randomised, controlled trial comparing neurally adjusted ventilatory assist to pressure support ventilation. Flow and the electrical activity of the diaphragm (EAdi) were recorded within 48 h of switching from controlled ventilation to a partial mode of ventilatory assistance. Variability of flow and EAdi-related variables were quantified by the coefficient of variation, the amplitude ratio of the spectrum's first harmonic to its zero-frequency component (H1/DC) and two surrogates of complexity. Main results 98 patients ventilated for a median duration of 5 days were included. H1/DC of inspiratory flow and EAdi were lower in survivors than in nonsurvivors, suggesting a higher breathing variability in this population (for flow, 37% versus 45%, p=0.041; for EAdi, 42% versus 52%, p=0.002). By multivariate analysis, H1/DC of inspiratory EAdi was independently associated with day-28 mortality (OR 1.10, p=0.002). H1/DC of inspiratory EAdi was lower in patients with a duration of mechanical ventilation

Question Human PHOX2B mutations result in life-threatening sleep-related hypoventilation (congenital central hypoventilation syndrome, CCHS). Most patients retain ventilatory activity when awake through a respiratory-related cortical network. We hypothesised that this need to mobilise cortical resources to breathe would lead to breathing-cognition interferences during cognitive loading. Patients and methods Seven adult CCHS patients (five women; median age 21) performed standard neuropsychological tests (paced auditory serial addition test – calculation capacity, working memory, sustained and divided attention; trail making test – visuospatial exploration capacity, cognitive processing speed, attentional flexibility; Corsi block-tapping test – visuospatial memory, short-term memory, working memory) during unassisted breathing and under ventilatory support. Ventilatory variables and transcutaneous haemoglobin oxygen saturation were recorded. Cortical connectivity changes between unassisted breathing and ventilatory support were assessed using electroencephalographic recordings (EEG). Results Baseline performances were lower than expected in individuals of this age. During unassisted breathing, cognitive loading coincided with increased breathing variability, and decreases in oxygen saturation inversely correlated with an increasing number of apnoeic cycles per minute (rho −0.46, 95% CI −0.76 to −0.06, p=0.01). During ventilatory support, cognitive tasks did not disrupt breathing pattern and were not associated with decreased oxygen saturation. Ventilatory support was associated with changes in EEG cortical connectivity but not with improved test performances. Conclusions Acute cognitive loads induce oxygen desaturation in adult CCHS patients during unassisted breathing, but not under ventilatory support. This justifies considering the use of ventilatory support during mental tasks in CCHS patients to avoid repeated episodes of hypoxia.

Abstract Background Whether sepsis-associated diaphragm dysfunction may improve despite the exposure of mechanical ventilation in critically ill patients is unclear. This study aims at describing the diaphragm function time course of septic and non-septic mechanically ventilated patients. Methods Secondary analysis of two prospective observational studies of mechanically ventilated patients in whom diaphragm function was assessed twice: within the 24 h after intubation and when patients were switched to pressure support mode, by measuring the endotracheal pressure in response to bilateral anterior magnetic phrenic nerve stimulation (Ptr,stim). Change in diaphragm function was expressed as the difference between Ptr,stim measured under pressure support mode and Ptr,stim measured within the 24 h after intubation. Sepsis was defined according to the Sepsis-3 international guidelines upon inclusion. In a sub-group of patients, the right hemidiaphragm thickness was measured by ultrasound. Results Ninety-two patients were enrolled in the study. Sepsis upon intubation was present in 51 (55%) patients. In septic patients, primary reason for ventilation was acute respiratory failure related to pneumonia (37/51; 73%). In non-septic patients, main reasons for ventilation were acute respiratory failure not related to pneumonia (16/41; 39%), coma (13/41; 32%) and cardiac arrest (6/41; 15%). Ptr,stim within 24 h after intubation was lower in septic patients as compared to non-septic patients: 6.3 (4.9–8.7) cmH2O vs. 9.8 (7.0–14.2) cmH2O (p = 0.004), respectively. The median (interquartile) duration of mechanical ventilation between first and second diaphragm evaluation was 4 (2–6) days in septic patients and 3 (2–4) days in non-septic patients (p = 0.073). Between first and second measurements, the change in Ptr,stim was + 19% (− 13–61) in septic patients and − 7% (− 40–12) in non-septic patients (p = 0.005). In the sub-group of patients with ultrasound measurements, end-expiratory diaphragm thickness decreased in both, septic and non-septic patients. The 28-day mortality was higher in patients with decrease or no change in diaphragm function. Conclusion Septic patients were associated with a more severe but reversible impaired diaphragm function as compared to non-septic patients. Increase in diaphragm function was associated with a better survival.

Abstract Purpose To describe health-related quality of life (HRQoL) and dyspnea of COVID-19, 2 and 12 months after an intensive care unit (ICU) stay. Methods Patients discharged from the ICU between April and June 2020 and subsequently transferred to an inpatient rehabilitation facility were assessed 2 months and 12 months after ICU admission. HRQoL was assessed by the EuroQoL EQ-5D-3L (visual analog scale and time trade-off normalized to the French population algorithm) and dyspnea was assessed by the modified Medical Research Council (mMRC) dyspnea scale. Results We enrolled 94 patients. Median EQ-5D-3L time trade-off was 0.80 (interquartile range, 0.36–0.91) at 2 months and 0.91 (0.52–1.00) at 12 months (P = 0.12). EQ-5D-3L visual analog scale was 70 (60–85) at 2 months and 70 (60–85) at 12 months (P = 0.07). The mMRC dyspnea scale was 3 (2–4) at ICU discharge, 1 (0–2), P

IntroductionCongenital Central Hypoventilation Syndrome, a rare disease caused by PHOX2B mutation, is associated with absent or blunted CO2/H+ chemosensitivity due to the dysfunction of PHOX2B neurons of the retrotrapezoid nucleus. No pharmacological treatment is available. Clinical observations have reported non-systematic CO2/H+ chemosensitivity recovery under desogestrel.MethodsHere, we used a preclinical model of Congenital Central Hypoventilation Syndrome, the retrotrapezoid nucleus conditional Phox2b mutant mouse, to investigate whether etonogestrel, the active metabolite of desogestrel, led to a restoration of chemosensitivity by acting on serotonin neurons known to be sensitive to etonogestrel, or retrotrapezoid nucleus PHOX2B residual cells that persist despite the mutation. The influence of etonogestrel on respiratory variables under hypercapnia was investigated using whole-body plethysmographic recording. The effect of etonogestrel, alone or combined with serotonin drugs, on the respiratory rhythm of medullary-spinal cord preparations from Phox2b mutants and wildtype mice was analyzed under metabolic acidosis. c-FOS, serotonin and PHOX2B were immunodetected. Serotonin metabolic pathways were characterized in the medulla oblongata by ultra-high-performance liquid chromatography.ResultsWe observed etonogestrel restored chemosensitivity in Phox2b mutants in a non-systematic way. Histological differences between Phox2b mutants with restored chemosensitivity and Phox2b mutant without restored chemosensitivity indicated greater activation of serotonin neurons of the raphe obscurus nucleus but no effect on retrotrapezoid nucleus PHOX2B residual cells. Finally, the increase in serotonergic signaling by the fluoxetine application modulated the respiratory effect of etonogestrel differently between Phox2b mutant mice and their WT littermates or WT OF1 mice, a result which parallels with differences in the functional state of serotonergic metabolic pathways between these different mice.DiscussionOur work thus highlights that serotonin systems were critically important for the occurrence of an etonogestrel-restoration, an element to consider in potential therapeutic intervention in Congenital Central Hypoventilation Syndrome patients.

Abstract Introduction Dyspnea is common and often severe symptom in mechanically ventilated patients. Proportional assist ventilation (PAV) is an assist ventilatory mode that adjusts the level of assistance to the activity of respiratory muscles. We hypothesized that PAV reduce dyspnea compared to pressure support ventilation (PSV). Patients and methods Mechanically ventilated patients with clinically significant dyspnea were included. Dyspnea intensity was assessed by the Dyspnea—Visual Analog Scale (D-VAS) and the Intensive Care-Respiratory Distress Observation Scale (IC-RDOS) at inclusion (PSV-Baseline), after personalization of ventilator settings in order to minimize dyspnea (PSV-Personalization), and after switch to PAV. Respiratory drive was assessed by record of electromyographic activity of inspiratory muscles, the proportion of asynchrony was analyzed. Results Thirty-four patients were included (73% males, median age of 66 [57–77] years). The D-VAS score was lower with PSV-Personalization (37 mm [20‒55]) and PAV (31 mm [14‒45]) than with PSV-Baseline (62 mm [28‒76]) (p

Background Dyspnea is a frightening and debilitating experience. It attracts less attention than pain (‘dyspnea invisibility’), possibly because of its non-universal nature. We tested the impact of self-induced experimental dyspnea on medical residents.Materials and Methods During a teaching session following the principles of experiential learning, emergency medicine residents were taught about dyspnea theoretically, observed experimental dyspnea in their teacher, and personally experienced self-induced dyspnea. The corresponding psychophysiological reactions were described. Immediate and 1-year evaluations were conducted to assess course satisfaction (overall 0–20 grade) and the effect on the understanding of what dyspnea represents for patients.Results Overall, 55 emergency medicine residents participated in the study (26 men, median age 26 years). They were moderately satisfied with previous dyspnea teaching (6 [5–7] on a 0–10 numerical rating scale [NRS]) and expressed a desire for an improvement in the teaching (8 [7–9]). Immediately after the course they reported improved understanding of patients’ experience (7 [6–8]), which persisted at 1 year (8 [7–9], 28 respondents). Overall course grade was 17/20 [15–18], and there were significant correlations with experimental dyspnea ratings (intensity: r = 0.318 [0.001–0.576], p = 0.043; unpleasantness: r = 0.492 [0.208–0.699], p = 0.001). In multivariate analysis, the only factor independently associated with the overall course grade was ‘experiential understanding’ (the experimental dyspnea-related improvement in the understanding of dyspneic patients’ experience). A separate similar experiment conducted in 50 respiratory medicine residents yielded identical results.Conclusions This study suggests that, in advanced medical residents, the personal discovery of dyspnea can have a positive impact on the understanding of what dyspnea represents for patients. This could help fight dyspnea invisibility.

Abstract Background Chronic Obstructive Pulmonary Disease (COPD) is one of the top 10 causes of death worldwide, representing a major public health problem. Researchers have been looking for new technologies and methods for patient monitoring with the intention of an early identification of acute exacerbation events. Many of these works have been focusing in breathing rate variation, while achieving unsatisfactory sensitivity and/or specificity. This study aims to identify breathing features that better describe respiratory pattern changes in a short-term adjustment of the load-capacity-drive balance, using exercising data. Results Under any tested circumstances, breathing rate alone leads to poor capability of classifying rest and effort periods. The best performances were achieved when using Fourier coefficients or when combining breathing rate with the signal amplitude and/or ARIMA coefficients. Conclusions Breathing rate alone is a quite poor feature in terms of prediction of breathing change and the addition of any of the other proposed features improves the classification power. Thus, the combination of features may be considered for enhancing exacerbation prediction methods based in the breathing signal.Trial Registration : ClinicalTrials NCT03753386. Registered 27 November 2018, https://clinicaltrials.gov/show/NCT03753386

Abstract Background Diaphragm dysfunction and weaning-induced pulmonary oedema are commonly involved during weaning failure, but their physiological interactions have been poorly reported. Our hypothesis was that diaphragm dysfunction is not particularly associated with weaning-induced pulmonary oedema. Methods It was a single-centre and physiological study conducted in patients who had failed a first spontaneous breathing trial and who underwent a second trial. The diaphragm function was evaluated by measuring the tracheal pressure generated in response to a bilateral magnetic phrenic nerves stimulations. Weaning-induced pulmonary oedema was diagnosed in case of failure of the spontaneous breathing trial if patients exhibited signs of plasma concentration or echocardiographic diagnosis of pulmonary artery occlusion pressure elevation. Results Fifty-three patients were included and 31/53 (58%) failed the spontaneous breathing trial, including 24/31 (77%) patients with weaning-induced pulmonary oedema. Diaphragm dysfunction was present in 33/53 (62%) patients. Diaphragm dysfunction or weaning-induced pulmonary oedema were present in 26/31 (84%) of the patients who failed the spontaneous breathing trial. Weaning-induced pulmonary oedema occurred in 20/33 (61%) patients with a diaphragm dysfunction and in 4/20 (20%) patients without (p = 0.005). Conclusion Weaning-induced pulmonary oedema was three times more frequent in case of diaphragm dysfunction. Even in case of diaphragm dysfunction, physicians might be encouraged to investigate the presence of weaning-induced pulmonary oedema during weaning failure.

Abstract Mechanical ventilation is a highly utilized life‐saving tool, particularly in the current era. The use of EEG in a brain–ventilator interface (BVI) to detect respiratory discomfort (due to sub‐optimal ventilator settings) would improve treatment in mechanically ventilated patients. This concept has been realized via development of an EEG covariance‐based classifier that detects respiratory‐related cortical activity associated with respiratory discomfort. The aim of this study was to determine if head movement, detected by an accelerometer, can detect and/or improve the detection of respiratory‐related cortical activity compared to EEG alone. In 25 healthy participants, EEG and acceleration of the head were recorded during loaded and quiet breathing in the seated and lying postures. Detection of respiratory‐related cortical activity using an EEG covariance‐based classifier was improved by inclusion of data from an Accelerometer‐based classifier, i.e. classifier ‘Fusion’. In addition, ‘smoothed’ data over 50s, rather than one 5 s window of EEG/Accelerometer signals, improved detection. Waveform averages of EEG and head acceleration showed the incidence of pre‐inspiratory potentials did not differ between loaded and quiet breathing, but head movement was greater in loaded breathing. This study confirms that compared to event‐related analysis with >5 min of signal acquisition, an EEG‐based classifier is a clinically valuable tool with rapid processing, detection times, and accuracy. Data smoothing would introduce a small delay (

Abstract Head-out water immersion alters respiratory compliance which underpins defining pressure at a “Lung centroid” and the breathing “Static Lung Load”. In diving medicine as in designing dive-breathing devices a single value of lung centroid pressure is presumed as everyone’s standard. On the contrary, we considered that immersed respiratory compliance is disparate among a homogenous adult group (young, healthy, sporty). We wanted to substantiate this ample scattering for two reasons: (i) it may question the European standard used in designing dive-breathing devices; (ii) it may contribute to understand the diverse individual figures of immersed work of breathing. Resting spirometric measurements of lung volumes and the pressure–volume curve of the respiratory system were assessed for 18 subjects in two body positions (upright Up, and supine Sup). Measurements were taken in air (Air) and with subjects immersed up to the sternal notch (Imm). Compliance of the respiratory system (Crs) was calculated from pressure–volume curves for each condition. A median 60.45% reduction in Crs was recorded between Up-Air and Up-Imm (1.68 vs 0.66 L/kPa), with individual reductions ranging from 16.8 to 82.7%. We hypothesize that the previously disregarded scattering of immersion-reduced respiratory compliance might participate to substantial differences in immersed work of breathing.

Abstract Background Diaphragm dysfunction is highly prevalent in mechanically ventilated patients. Recent work showed that changes in diaphragm shear modulus (ΔSMdi) assessed using ultrasound shear wave elastography (SWE) are strongly related to changes in Pdi (ΔPdi) in healthy subjects. The aims of this study were to investigate the relationship between ΔSMdi and ΔPdi in mechanically ventilated patients, and whether ΔSMdi is responsive to change in respiratory load when varying the ventilator settings. Methods A prospective, monocentric study was conducted in a 15-bed ICU. Patients were included if they met the readiness-to-wean criteria. Pdi was continuously monitored using a double-balloon feeding catheter orally introduced. The zone of apposition of the right hemidiaphragm was imaged using a linear transducer (SL10-2, Aixplorer, Supersonic Imagine, France). Ultrasound recordings were performed under various pressure support settings and during a spontaneous breathing trial (SBT). A breath-by-breath analysis was performed, allowing the direct comparison between ΔPdi and ΔSMdi. Pearson’s correlation coefficients (r) were used to investigate within-individual relationships between variables, and repeated measure correlations (R) were used for determining overall relationships between variables. Linear mixed models were used to compare breathing indices across the conditions of ventilation. Results Thirty patients were included and 930 respiratory cycles were analyzed. Twenty-five were considered for the analysis. A significant correlation was found between ΔPdi and ΔSMdi (R = 0.45, 95% CIs [0.35 0.54], p 0.06). Changing the condition of ventilation similarly affected ΔPdi and ΔSMdi. Patients in which ΔPdi–ΔSMdi correlation was non-significant had a faster respiratory rate as compared to that of patient with a significant ΔPdi–ΔSMdi relationship (median (Q1–Q3), 25 (18–33) vs. 21 (15–26) breaths.min−1, respectively). Conclusions We demonstrate that ultrasound SWE may be a promising surrogate to Pdi in mechanically ventilated patients. Respiratory rate appears to negatively impact SMdi measurement. Technological developments are needed to generalize this method in tachypneic patients. Trial registration NCT03832231 .

Abstract Background Intensive care unit (ICU)-acquired weakness and diaphragm dysfunction are frequent conditions, both associated with poor prognosis in critically ill patients. While it is well established that ICU-acquired weakness severely impairs long-term prognosis, the association of diaphragm dysfunction with this outcome has never been reported. This study investigated whether diaphragm dysfunction is associated with negative long-term outcomes and whether the coexistence of diaphragm dysfunction and ICU-acquired weakness has a particular association with 2-year survival and health-related quality of life (HRQOL). Methods This study is an ancillary study derived from an observational cohort study. Patients under mechanical ventilation were enrolled at the time of their first spontaneous breathing trial. Diaphragm dysfunction was defined by tracheal pressure generated by phrenic nerve stimulation

Background: Identification of prognostic factors in COVID-19 remains a global challenge. The role of smoking is still controversial.Methods: PCR-positive in- and outpatients with symptomatic COVID-19 from a large French University hospital were systematically interviewed for their smoking status, use of e-cigarette, and nicotinic substitutes. The rates of daily smokers in in- and outpatients were compared using the same smoking habit questionnaire to those in the 2019 French general population, after standardisation for sex and age.Results: The inpatient group was composed of 340 patients, median age of 66 years: 203 men (59.7%) and 137 women (40.3%), median age of both 66 years, with a rate of 4.1% daily smokers (CI 95% [2.3–6.9]) (5.4% of men and 2.2% of women). The outpatient group was composed of 139 patients, median age of 44 years: 62 men (44.6%, median age of 43 years) and 77 women (55.4%, median age of 44 years). The daily smoker rate was 6.1% (CI 95% [2.7–11.6], 5.1% of men and 6.8% of women). Amongst inpatients, daily smokers represented 2.2 and 3.4% of the 45 dead patients and of the 29 patients transferred to ICU, respectively. The rate of daily smokers was significantly lower in patients with symptomatic COVID-19, as compared to that in the French general population after standardisation by age and sex, with standardised incidence ratios (SIRs) of 0.24 [0.12–0.48] for outpatients and 0.24 [0.14–0.40] for inpatients.Conclusions: Daily smoker rate in patients with symptomatic COVID-19 is lower as compared to the French general population

Abstract Background Noninvasive ventilation (NIV) is the application of mechanical ventilation through a mask. It is used to treat certain forms of acute respiratory failure in intensive care units (ICU). NIV has clinical benefits but can be anxiogenic for the patients. This study aimed at describing cognitive and affective attitudes toward NIV among patients experiencing NIV for the first time in the context of an ICU stay. Methods Semi-structured interviews were conducted in 10 patients during their ICU stay and soon after their first NIV experience. None of the patients had ever received NIV previously. Evaluative assertion analysis and thematic analysis were used to investigate cognitive and affective attitudes toward NIV before, during, and after the first NIV experience, as well as patient attitudes toward caregivers and relatives. Results Before their first NIV session, the cognitive attitudes of the patients were generally positive. They became less so and more ambiguous during and after NIV, as the patients discovered the actual barriers associated with NIV. Affective attitudes during NIV were more negative than affective attitudes before and after NIV, with reports of dyspnea, anxiety, fear, claustrophobic feelings, and reactivation of past traumatic experiences. The patients had more positive attitudes toward the presence of a caregiver during NIV, compared to the presence of a family member. Conclusion This study corroborates the possibly negative—or even traumatic—nature of the NIV experience, with emphasis on the role of affective attitudes. This is a rationale for evaluating the impact of NIV-targeted psychological interventions in ICU patients with acute respiratory failure.

Summary: Heart rate has natural fluctuations that are typically ascribed to autonomic function. Recent evidence suggests that conscious processing can affect the timing of the heartbeat. We hypothesized that heart rate is modulated by conscious processing and therefore dependent on attentional focus. To test this, we leverage the observation that neural processes synchronize between subjects by presenting an identical narrative stimulus. As predicted, we find significant inter-subject correlation of heart rate (ISC-HR) when subjects are presented with an auditory or audiovisual narrative. Consistent with our hypothesis, we find that ISC-HR is reduced when subjects are distracted from the narrative, and higher ISC-HR predicts better recall of the narrative. Finally, patients with disorders of consciousness have lower ISC-HR, as compared to healthy individuals. We conclude that heart rate fluctuations are partially driven by conscious processing, depend on attentional state, and may represent a simple metric to assess conscious state in unresponsive patients.

Background Whereas first-line bronchial artery embolisation (BAE) is considered standard of care for the management of severe haemoptysis, it is unknown whether this approach is warranted for non-severe haemoptysis.Research question To assess the efficacy on bleeding control and the safety of first-line BAE in non-severe haemoptysis of mild abundance.Study design and methods This multicentre, randomised controlled open-label trial enrolled adult patients without major comorbid condition and having mild haemoptysis (onset

Abstract Background Intensive care unit (ICU)-acquired weakness (ICU-AW) and ICU-acquired diaphragm dysfunction (ICU-DD) occur frequently in mechanically ventilated (MV) patients. It is unknown whether they have different risk factors and different impacts on outcome. This study was designed to (1) describe the respective risk factors associated with ICU-AW and severe ICU-DD and (2) evaluate the respective impact of ICU-AW and severe ICU-DD on outcome. Methods Post hoc analysis of two prospective cohort studies conducted in two ICUs. In patients mechanically ventilated for at least 24 h undergoing a first spontaneous breathing trial, severe ICU-DD was defined as diaphragm twitch pressure

Abstract Background Mechanical ventilation (MV) is a life-saving technology that restores or assists breathing. Like any treatment, MV has side effects. In some patients it can cause diaphragmatic atrophy, injury, and dysfunction (ventilator-induced diaphragmatic dysfunction, VIDD). Accumulating evidence suggests that VIDD makes weaning from MV difficult, which involves increased morbidity and mortality. Methods and analysis This paper describes the protocol of a randomized, controlled, open-label, multicenter trial that is designed to investigate the safety and effectiveness of a novel therapy, temporary transvenous diaphragm pacing (TTVDP), to improve weaning from MV in up to 88 mechanically ventilated adult patients who have failed at least two spontaneous breathing trials over at least 7 days. Patients will be randomized (1:1) to TTVDP (treatment) or standard of care (control) groups. The primary efficacy endpoint is time to successful extubation with no reintubation within 48 h. Secondary endpoints include maximal inspiratory pressure and ultrasound-measured changes in diaphragm thickness and diaphragm thickening fraction over time. In addition, observational data will be collected and analyzed, including 30-day mortality and time to discharge from the intensive care unit and from the hospital. The hypothesis to be tested postulates that more TTVDP patients than control patients will be successfully weaned from MV within the 30 days following randomization. Discussion This study is the first large-scale clinical trial of a novel technology (TTVDP) aimed at accelerating difficult weaning from MV. The technology tested provides the first therapy directed specifically at VIDD, an important cause of delayed weaning from MV. Its results will help delineate the place of this therapeutic approach in clinical practice and help design future studies aimed at defining the indications and benefits of TTVDP. Trial registration ClinicalTrials.gov, NCT03096639. Registered on 30 March 2017.

Sleep-related breathing disorders, including sleep apnea and hypoxemia during sleep, are common in pulmonary arterial hypertension, but the underlying mechanisms remain unknown. Overnight fluid shift from the legs to the upper airway and to the lungs promotes obstructive and central sleep apnea, respectively, in fluid-retaining states. The main objective was to evaluate if overnight rostral fluid shift from the legs to the upper part of the body is associated with sleep-related breathing disorders in pulmonary arterial hypertension. In a prospective study, a group of stable patients with idiopathic, heritable, related to drugs, toxins, or treated congenital heart disease pulmonary arterial hypertension underwent a polysomnography and overnight fluid shift measurement by bioelectrical impedance in the month preceding or following a one-day hospitalization according to regular pulmonary arterial hypertension follow-up schedule with a right heart catheterization. Results show that among 15 patients with pulmonary arterial hypertension (women: 87%; median (25–75th percentiles); age: 40 (32–61) years; mean pulmonary arterial pressure 56 (46–68) mmHg; pulmonary vascular resistance 8.8 (6.4–10.1) Wood units), two patients had sleep apnea and eight (53%) had hypoxemia during sleep without apnea. The overnight rostral fluid shift was 168 (118–263) mL per leg. Patients with hypoxemia during sleep had a greater fluid shift (221 (141– 361) mL) than those without hypoxemia (118 (44–178) mL, p = 0.045). In conclusion, this pilot study suggests that hypoxemia during sleep is associated with overnight rostral fluid shift in pulmonary arterial hypertension.

Obstructive sleep apnea syndrome (OSAS) is associated with postural dysfunction characterized by abnormal spinal curvature and disturbance of balance and walking, whose pathophysiology is poorly understood. We hypothesized that it may be the result of a pathological interaction between postural and ventilatory functions. Twelve patients with OSAS (4 women, age 53 years [51–63] (median [quartiles]), apnea hypopnea index 31/h [24–41]) were compared with 12 healthy matched controls. Low dose biplanar X-rays (EOS® system) were acquired and personalized three-dimensional models of the spine and pelvis were reconstructed. We also estimated posturo-respiratory coupling by measurement of respiratory emergence, obtaining synchronized center of pressure data from a stabilometric platform and ventilation data recorded by an optico-electronic system of movement analysis. Compared with controls, OSAS patients, had cervical hyperextension with anterior projection of the head (angle OD-C7 12° [8; 14] vs. 5° [4; 8]; p = 0.002), and thoracic hyperkyphosis (angle T1–T12 65° [51; 71] vs. 49° [42; 59]; p = 0.039). Along the mediolateral axis: (1) center of pressure displacement was greater in OSAS patients, whose balance was poorer (19.2 mm [14.2; 31.5] vs. 8.5 [1.4; 17.8]; p = 0.008); (2) respiratory emergence was greater in OSAS patients, who showed increased postural disturbance of respiratory origin (19.2% [9.9; 24.0] vs. 8.1% [6.4; 10.4]; p = 0.028). These results are evidence for the centrally-mediated and primarily respiratory origin of the postural dysfunction in OSAS. It is characterized by an hyperextension of the cervical spine with a compensatory hyperkyphosis, and an alteration in posturo-respiratory coupling, apparently secondary to upper airway instability.

Abstract Background Diaphragm dysfunction is defined by a value of twitch tracheal pressure in response to magnetic phrenic stimulation (twitch pressure) amounting to less than 11 cmH2O. This study assessed whether this threshold or a lower one would predict accurately weaning failure from mechanical ventilation. Twitch pressure was compared to ultrasound measurement of diaphragm function. Methods In patients undergoing a first spontaneous breathing trial, diaphragm function was evaluated by twitch pressure and by diaphragm ultrasound (thickening fraction). Receiver operating characteristics curves were computed to determine the best thresholds predicting failure of spontaneous breathing trial. Results Seventy-six patients were evaluated, 48 (63%) succeeded and 28 (37%) failed the spontaneous breathing trial. The optimal thresholds of twitch pressure and thickening fraction to predict failure of the spontaneous breathing trial were, respectively, 7.2 cmH2O and 25.8%, respectively. The receiver operating characteristics curves were 0.80 (95% CI 0.70–0.89) for twitch pressure and 0.82 (95% CI 0.73–0.93) for thickening fraction. Both receiver operating characteristics curves were similar (p = 0.83). A twitch pressure value lower than 11 cmH2O (the traditional cutoff for diaphragm dysfunction) predicted failure of the spontaneous breathing trial with a sensitivity of 89% (95% CI 72–98%) and a specificity of 45% (95% CI 30–60%). Conclusions Failure of spontaneous breathing trial can be predicted with a lower value of twitch pressure than the value defining diaphragm dysfunction. Twitch pressure and thickening fraction had similar strong performance in the prediction of failure of the spontaneous breathing trial.

Abstract Background Osteopathic manipulative treatment (OMT) of the sphenopalatine ganglion (SPG) is used empirically for the treatment of rhinitis and snoring and is thought to increase pharyngeal stability. This trial was designed to study the effects of this treatment on pharyngeal stability evaluated by critical closing pressure in obstructive sleep apnoea syndrome. Methods This single-centre, randomized, crossover, double-blind study compared active manipulation and sham manipulation of the SPG. Randomization was computer-generated. Patients each received one active manipulation and one sham manipulation at an interval of 21 days and were evaluated 30 min and 48 h after each session administered by a qualified osteopath. Neither the patients, nor the investigator performing the evaluations were informed about the order of the two techniques (double-blind). The primary endpoint was the percentage of responding patients presenting increased pharyngeal stability defined by a variation of critical closing pressure (Pcrit) of at least −4 cmH2O at 30 min. Secondary endpoints were the variation of Pcrit in absolute values, sleepiness and snoring. Others endpoints were lacrimation (Schirmer’s test), induced pain, sensations experienced during OMT. Results Ten patients were included and nine (57 [50; 58] years, comprising 7 men, with an apnoea-hypopnoea index of 31.0 [25.5; 33.2]/h; (values are median [quartiles])) were analysed. Seven patients were analysed for the primary endpoint and nine patients were analysed for secondary endpoints. Five patients responded after active manipulation versus no patients after sham manipulation (p = 0.0209). Active manipulation induced more intense pain (p = 0.0089), increased lacrimation (ns) and more tactile, nociceptive and gustatory sensations (13 versus 1) compared to sham manipulation. No significant difference was observed for the other endpoints. Conclusions Osteopathic manipulative treatment of the SPG may improve pharyngeal stability in obstructive sleep apnoea syndrome. This trial validates the feasibility of the randomized, controlled, double-blind methodology for evaluation of this osteopathic treatment. Studies on a larger sample size must specify the efficacy on the apnoea-hypopnoea index. Trial registration The study was retrospectively registered in the clinicaltrial.gov registry under reference NCT01193738 on 1st September 2010 (first inclusion May 19, 2010).

Abstract Background Poor sleep is common in intensive care unit (ICU) patients, where environmental factors contribute to reduce and fragment sleep. The objective of this study was to evaluate the impact of earplugs and eye mask on sleep architecture in ICU patients. Methods A single-center randomized controlled trial of 64 ICU patients was conducted from July 2012 to December 2013. Patients were randomly assigned to sleep with or without earplugs and an eye mask from inclusion until ICU discharge. Polysomnography was performed on the first day and night following inclusion. The primary outcome was the proportion of stage N3 sleep over total sleep time. Secondary outcomes were other descriptors of sleep and major outcome variables. Results In the intervention group, nine (30%) patients did not wear earplugs all night long. The proportion of N3 sleep was 21 [7–28]% in the intervention group and 11 [3–23]% in the control group (p = 0.09). The duration of N3 sleep was higher among the patients in the intervention group who wore earplugs all night long than in the control group (74 [32–106] vs. 31 [7–76] minutes, p = 0.039). The number of prolonged awakenings was smaller in the intervention group (21 [19–26] vs. 31 [21–47] in the control group, p = 0.02). No significant difference was observed between the two groups in terms of clinical outcome variables. Conclusions Earplugs and eye mask reduce long awakenings and increase N3 duration when they are well tolerated. Trial registration ClinicalTrials.gov, NCT02292134. Registered on 21 Nov 2013.

Characterizing the breathing pattern in naturally breathing humans brings important information on respiratory mechanics, respiratory muscle, and breathing control. However, measuring breathing modifies breathing (observer effect) through the effects of instrumentation and awareness: measuring human breathing under true ecological conditions is currently impossible. This study tested the hypothesis that non-contact vibrometry using airborne ultrasound (SONAR) could measure breathing movements in a contactless and invisible manner. Thus, first, we evaluated the validity of SONAR measurements by testing their interchangeability with pneumotachograph (PNT) measurements obtained at the same time. We also aimed at evaluating the observer effect by comparing breathing variability obtained by SONAR versus SONAR-PNT measurements. Twenty-three healthy subjects (12 men and 11 women; mean age 33 years – range: 20–54) were studied during resting breathing while sitting on a chair. Breathing activity was described in terms of ventilatory flow measured using a PNT and, either simultaneously or sequentially, with a SONAR device measuring the velocity of the surface motion of the chest wall. SONAR was focused either anteriorly on the xiphoid process or posteriorly on the lower part of the costal margin. Discrete ventilatory temporal and volume variables and their coefficients of variability were calculated from the flow signal (PNT) and the velocity signal (SONAR) and tested for interchangeability (Passing-Bablok regression). Tidal volume (VT) and displacement were linearly related. Breathing frequency (BF), total cycle time (TT), inspiratory time (TI), and expiratory time (TE) met interchangeability criteria. Their coefficients of variation were not statistically significantly different with PNT and SONAR-only. This was true for both the anterior and the posterior SONAR measurements. Non-contact vibrometry using airborne ultrasound is a valid tool for measuring resting breathing pattern.

The maintenance of upright balance in healthy humans requires the preservation of a horizontal gaze, best achieved through dynamical adjustments of spinal curvatures and a pelvic tilt that keeps the head-to-pelvis alignment close to vertical. It is currently unknown whether the spinal and pelvic compensations of respiratory-related postural perturbations are associated with preservation of the head-to-pelvis vertical alignment. We tested this hypothesis by comparing postural alignment variables at extreme lung volume (total lung capacity, TLC; residual volume, RV) with their reference value at functional residual capacity (FRC). Forty-eight healthy subjects [22 women; median age of 34 (26; 48) years] were studied using low dose biplanar X-rays (BPXR; EOS®system). Personalized three-dimensional models of the spine and pelvis were reconstructed at the three lung volumes. Extreme lung volumes were associated with changes of thoracic curvature bringing it outside the normal range. Maximal inspiration reduced thoracic kyphosis [T1–T12 angle = 47° (37; 56), -4° variation (-9; 1), p = 0.0007] while maximal expiration induced hyperkyphosis [T1–T12 angle = 63° (55; 68); +10° variation (5; 12), p = 9 × 10-12]. Statistically significant (all p < 0.01) cervical and pelvic compensatory changes occurred [C3–C7 angle: +4° (-2; 11) and pelvic tilt +1° (0; 3) during maximal inspiration; C3–C7 angle: -7° (-18; -1) and pelvic tilt +5° (1; 8) during maximal expiration], resulting in preserved head-to-pelvis alignment (no change in the angle between the vertical plane and the line connecting the odontoid process and the midpoint of the line connecting the center of the two femoral heads ODHA). Lung volume related postural perturbations were more marked as a function of age, but age did not affect the head-to-pelvis alignment. These findings should help understand balance alterations in patients with chronic respiratory diseases that modify lung volume and rib cage geometry.

Patients with central respiratory paralysis can benefit from diaphragm pacing to restore respiratory function. However, it would be important to develop a continuous respiratory monitoring method to alert on apnea occurrence, in order to improve the efficiency and safety of the pacing system. In this study, we present a preliminary validation of an acoustic apnea detection method on healthy subjects data. Thirteen healthy participants performed one session of two 2-min recordings, including a voluntary respiratory pause. The recordings were post-processed by combining temporal and frequency detection domains, and a new method was proposed—Phonocardiogram-Derived Respiration (PDR). The detection results were compared to synchronized pneumotachograph, electrocardiogram (ECG), and abdominal strap (plethysmograph) signals. The proposed method reached an apnea detection rate of 92.3%, with 99.36% specificity, 85.27% sensitivity, and 91.49% accuracy. PDR method showed a good correlation of 0.77 with ECG-Derived Respiration (EDR). The comparison of R-R intervals and S-S intervals also indicated a good correlation of 0.89. The performance of this respiratory detection algorithm meets the minimal requirements to make it usable in a real situation. Noises from the participant by speaking or from the environment had little influence on the detection result, as well as body position. The high correlation between PDR and EDR indicates the feasibility of monitoring respiration with PDR.

Speech or programmed sentences must often be interrupted in order to listen to and interact with interlocutors. Among many processes that produce such complex acts, the brain must precisely adjust breathing to produce adequate phonation. The mechanism of these adjustments is multifactorial and still poorly understood. In order to selectively examine the adjustment in breath control, we recorded respiratory-related premotor cortical potentials from the scalp of human subjects while they performed a single breathing initiation or inhibition task. We found that voluntary breathing is initiated if, and only if, the cortical premotor potential activity reaches a threshold activation level. The stochastic variability in the threshold correlates to the distribution of initiation times of breathing. The data also fitted a computerized interactive race model. Modeling results confirm that this model is also as effective in respiratory modality, as it has been found to be for eye and hand movements. No modifications were required to account for respiratory cycle inhibition processes. In this overly simplified task, we showed a link between voluntary initiation and control of breathing and activity in a fronto-median region of the cerebral cortex. These results shed light on some of the physiological constraints involved in the complex mechanisms of respiration, phonation, and language.

Respiratory-related premotor potentials from averaged electroencephalography (EEG) over the motor areas indicate cortical activation in healthy participants to maintain ventilation in the face of moderate inspiratory or expiratory loads. These experimental conditions are associated with respiratory discomfort, i.e., dyspnea. Premotor potentials are also observed in resting breathing in patients with reduced automatic respiratory drive or respiratory muscle strength due to respiratory or neurological disease, presumably in an attempt to maintain ventilation. The aim of this study was to determine if small voluntary increases in ventilation or smaller load-capacity imbalances, that generate an awareness of breathing but aren’t necessarily dyspneic, give rise to respiratory premotor potentials in healthy participants. In 15 healthy subjects, EEG was recorded during voluntary large breaths (∼3× tidal volume, that were interspersed with smaller non-voluntary breaths in the same trial; in 10 subjects) and breathing with a ‘low’ inspiratory threshold load (∼7 cmH2O; in 8 subjects). Averaged EEG signals at Cz and FCz were assessed for premotor potentials prior to inspiration. Premotor potential incidence in large breaths was 40%, similar to that in the smaller non-voluntary breaths in the same trial (20%; p > 0.05) and to that in a separate trial of resting breathing (0%; p > 0.05). The incidence of premotor potentials was 25% in the low load condition, similar to that in resting breathing (0%; p > 0.05). In contrast, voluntary sniffs were always associated with a higher incidence of premotor potentials (100%; p < 0.05). We have demonstrated that in contrast to respiratory and neurological disease, there is no significant cortical contribution to increase tidal volume or to maintain the load-capacity balance with a small inspiratory threshold load in healthy participants as detected using event-related potential methodology. A lack of cortical contribution during loading was associated with low ratings of respiratory discomfort and minimal changes in ventilation. These findings advance our understanding of the neural control of breathing in health and disease and how respiratory-related EEG may be used for medical technologies such as brain-computer interfaces.

Background: Predicting outcome after index admission in the ICU for COPD-related acute hypercapnic respiratory failure (AHRF) is difficult. Simple tools to stratify this risk and to promote interventions to mitigate it are needed.Aim: To prospectively evaluate the ability of severe dyspnea (NYHAIII-IV) to predict hospital readmission or death in COPD patients surviving AHRF in the ICU.Methods: 50 consecutive COPD patients were recruited from a larger cohort of patients (n = 78) surviving AHRF in the ICU. All predictive variables were collected within 15 days after resolution of respiratory failure before hospital discharge. COPD was diagnosed by spirometry. Heart failure was diagnosed with clinical rules and echocardiography. NYHA was measured upon hospital discharge. Hospital readmission and death were recorded at regular intervals for 3 months.Results: 21/50 (42%) COPD patients died or were readmitted to the hospital during the observation period: 12 out of the 20 NYHA III-IV patients (60%) and 8 out of the 28 NYHA I-II patients (29%). NYHA III-IV was associated with risk of readmission or death (univariate HR: 2.73, IC95: 1.11–6.69, p = 0.028). After controlling for age, FEV1, heart failure and BMI, NYHA III-IV remained associated with readmission or death (multivariate HR: 2.71, IC95: 1.06–6.93, p = 0.038).Conclusions: Our findings suggest that severe dyspnea measured upon hospital discharge in COPD patients surviving AHRF can stratify patient's risk of 3-month readmission or death.

BACKGROUND:Short-term mechanical ventilation (MV) protects against sepsis-induced diaphragmatic dysfunction. Prolonged MV induces diaphragmatic dysfunction in non-septic animals, but few reports describe the effects of prolonged MV in sepsis. We hypothesized that prolonged MV is not protective but worsens the diaphragmatic dysfunction induced by a mild sepsis, because MV and sepsis share key signaling mechanisms, such as cytokine upregulation. METHOD:We studied the impact of prolonged MV (12 h) in four groups (n = 8) of male Wistar rats: 1) endotoxemia induced by intraperitoneal injection of Escherichia coli lipopolysaccharide, 2) MV without endotoxemia, 3) combination of endotoxemia and MV and 4) sham control. Diaphragm mechanical performance, pro-inflammatory cytokine concentrations (Tumor Necrosis Factor-α, Interleukin-1β, Interleukin-6) in plasma were measured. RESULTS:Prolonged MV and sepsis independtly reduced maximum diaphragm force (-27%, P = 0.003; -37%, P

Diaphragm pacing allows certain quadriplegic patients to be weaned from mechanical ventilation. Pacing failure can result from device dysfunction, neurotransmission failure, or degraded lung mechanics (such as atelectasis). We report two cases where progressive pacing failure was attributed to deteriorated chest wall mechanics. The first patient suffered from cervical spinal cord injury at age 45, was implanted with a phrenic stimulator (intrathoracic), successfully weaned from ventilation, and permanently paced for 7 years. Pacing effectiveness then slowly declined, finally attributed to rib cage stiffening due to ankylosing spondylitis. The second patient became quadriplegic after meningitis at age 15, was implanted with a phrenic stimulator (intradiaphragmatic) and weaned. After a year hypoventilation developed without obvious cause. In relationship with complex endocrine disorders, the patient had gained 31 kg. Pacing failure was attributed to excessive mechanical inspiratory load. Rib cage mechanics abnormalities should be listed among causes of diaphragm pacing failure and it should be kept in mind that a “good diaphragm” is not sufficient to produce a “good inspiration”.

The aim of this study was to evaluate the feasibility of unilateral diaphragmatic reinnervation in humans by the inferior laryngeal nerve. This pilot study included chronically ventilated tetraplegic patients with destruction of phrenic nerve motoneurons. Five patients were included. They all had a high level of tetraplegia, with phrenic nerve motor neuron destruction. They were highly dependent on ventilation, without any possibility of weaning. They did not have other chronic pathologies, especially laryngeal disease. They all had diaphragmatic explorations to diagnose the destruction of the motoneurons of the phrenic nerves and nasoendoscopy to be sure that they did not have laryngeal or pharyngeal disease. Then, surgical anastomosis of the right phrenic nerve was performed with the inferior laryngeal nerve, by a cervical approach. A laryngeal reinnervation was performed at the same time, using the ansa hypoglossi. One patient was excluded because of a functional phrenic nerve and one patient died 6 months after the surgery of a cardiac arrest. The remaining three patients were evaluated after the anastomosis every 6 months. They did not present any swallowing or vocal alterations. In these three patients, the diaphragmatic explorations showed that there was a recovery of the diaphragmatic electromyogram of the right and left hemidiaphragms after 1 year. Two patients had surgical diaphragmatic explorations for diaphragmatic pacing 18–24 months after the reinnervation with excellent results. At 36 months, none of the patients could restore their automatic ventilation. In conclusion, this study demonstrated that diaphragmatic reinnervation by the inferior laryngeal nerve is effective, without any vocal or swallowing complications.